4LN0

Crystal structure of the VGLL4-TEAD4 complex

Summary for 4LN0

• Entry DOI: 10.2210/pdb4ln0/pdb
• Descriptor: Transcriptional enhancer factor TEF-3, Transcription cofactor vestigial-like protein 4, DI(HYDROXYETHYL)ETHER, ... (5 entities in total)
• Functional Keywords: tea/atts domain family, vestigial/tondu family, transcription factor, transcription cofactor, development, transcription
• Biological source: Mus musculus (mouse); More
• Cellular location: Nucleus: Q62296; Nucleus (By similarity): Q80V24
• Total number of polymer chains: 3
• Total formula weight: 58678.17

Authors

Wang, H.,Shi, Z.,Zhou, Z. (deposition date: 2013-07-11, release date: 2014-02-26, Last modification date: 2023-11-08)

Primary citation

Jiao, S.,Wang, H.,Shi, Z.,Dong, A.,Zhang, W.,Song, X.,He, F.,Wang, Y.,Zhang, Z.,Wang, W.,Wang, X.,Guo, T.,Li, P.,Zhao, Y.,Ji, H.,Zhang, L.,Zhou, Z.
A Peptide Mimicking VGLL4 Function Acts as a YAP Antagonist Therapy against Gastric Cancer.
Cancer Cell, 25:166-180, 2014

PubMed Abstract: The Hippo pathway has been implicated in suppressing tissue overgrowth and tumor formation by restricting the oncogenic activity of YAP. However, transcriptional regulators that inhibit YAP activity have not been well studied. Here, we uncover clinical importance for VGLL4 in gastric cancer suppression and find that VGLL4 directly competes with YAP for binding TEADs. Importantly, VGLL4's tandem Tondu domains are not only essential but also sufficient for its inhibitory activity toward YAP. A peptide mimicking this function of VGLL4 potently suppressed tumor growth in vitro and in vivo. These findings suggest that disruption of YAP-TEADs interaction by a VGLL4-mimicking peptide may be a promising therapeutic strategy against YAP-driven human cancers.

PubMed: 24525233
DOI: 10.1016/j.ccr.2014.01.010

Experimental method

X-RAY DIFFRACTION (2.896 Å)